48-Week Efficacy and Safety Results of Simplification to Single Agent Lopinavir

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KalMo: Study Design. Nunes EP. et al., twelfth EACS, Dublin, Ireland, November 2005; PE7.5/1. Section criteria HIV-1 RNA < 80 duplicates/mL for > 6 months No Hx of virological disappointment CD4 > 200 cells/mm3 CD4 nadir > 100 cells/mm3. Essential study endpoint Viral Load <80 duplicates/ml by week 48Virological disappointment: affirmed HIV-1 RNA > 1,000 duplicates/mL.

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Oral Presentation #TUAB0102 48-Week Efficacy and Safety Results of Simplification to Single Agent Lopinavir/ritonavir (LPV/r) Regimen in Patients Suppressed Below 80 duplicates/mL on HAART - The KalMo Study Nunes EP 1 , Oliveira MS 2 , Almeida MMTB 1 , Pilotto JH 2 , Ribeiro JE 2 , Faulhaber JC 1 , Norton M 3 , Zajdenverg R 1 , Schechter M 1 Projeto Praça Onze – UFRJ, 2 Hospital Geral de Nova Iguaçu – Rio de Janeiro, Brazil; 3 Abbott Laboratories, North Chicago, IL, USA

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KalMo: Study Design Entry criteria HIV-1 RNA < 80 duplicates/mL for > 6 months No Hx of virological disappointment CD4 > 200 cells/mm 3 CD4 nadir > 100 cells/mm 3 LPV/r SGC 400/100 mg BID Mono (n = 30) N=60 Randomized 1:1 Open mark 2 focuses in Brazil 96 weeks Maintain current regimen HAART (n = 30) HIV-1 RNA measured at Week 0, 4, 12, and q12 from that point Primary review endpoint Viral Load <80 duplicates/ml by week 48 Virological disappointment : affirmed HIV-1 RNA > 1,000 duplicates/mL Nunes EP. et al ., 12 th EACS, Dublin, Ireland, November 2005; PE7.5/1

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Demographics and Baseline Characteristics LPV/r SGC (n=30) Control (n=30) Gender Male Age (years) mean (range) Race/ethnicity Caucasian Black Other HIV-1 RNA (c/mL) CD4 check (cells/mm 3 ) mean (range) Hepatitis C Hepatitis B 17 (54.8%) 38.6 (20-61) 10 (33%) 4 (13.5%) 16 (53/5%) < 80 c/mL 552.6 (232-926) 3 0 20 (69%) 40.1 (25-64 ) 9 (30%) 5 (16.5%) 16 (53.5%) < 80 c/mL 514.3 (198-1021) 1 0 Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Prior ARV Treatment * All patients were accepting 2 NRTIs ** Only 1 persistent with LPV/r SGC Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Subject Disposition through 48 Weeks 60 subjects 30 subjects randomized to LPV/r monotherapy 30 subjects randomized to stay on their earlier regimen 0 randomized, not dosed* 1 randomized, not dosed 29 subjects randomized and stayed on earlier regimen 30 subjects randomized and dosed on LPV/r monotherapy 3 stops 1 virologic disappointment (w36) 1 detainment (w2) 1 pregnancy (w36) 2 cessations 1 review 3 looseness of the bowels 1 pregnancy (w4) 26 proceed on control regiment 28 proceed on LPV/r monotherapy Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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HIV-1 RNA < 80 duplicates/mL (ITT: NC=F) 86% 83% % with HIV-1 RNA < 80 c/mL Sample Size LPV/r monoRx Control 30 Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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HIV-1 RNA < 80 duplicates/mL (OT) 96% 92% Sample Size LPV/r monoRx Control 30 28 26

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Sample Size LPV/r monoRx Control 30 28 26 Change in Mean CD4 Cell Count from Baseline to Week 48 (cells/mm 3 ) 541 528 p-esteem = 0.799 CD4 Cell Count (cells/mm 3 ) Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Virologic Failures and Low-level Viremia Through Week 48 LPV/r Control Patients dosed Virologic Failures (%) Week of occurence Genotype Management Outcome Low level Viremia (%) HIV-1 RNA Occurrence Outcome 30 1 (3%) 48 No Mutations d/c, include TDF+3TC < 80 c/mL after 4 wks 1 (3%) 220-850 c/mL From Wk 24 to 48 < 80 c/mL from Wk 60 to Wk 96 29 1 (3%) 36 No Mutations d/c N/A 1 (3%) 98 c/mL Once (Wk 48) < 80 cp/mL from Wk 60

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LPV/r monotherapy 29-Nov-04 LPV/r + TDF + 3TC 11-Jan-06 Adherence (cases number) 100% w4 95.8% w12 100% w24 97% w36 100% w48 Patient 1 – Virologic Failure 800 2000 1800 CD4 (cells/mm3) 700 WT infection Viral Load (cp/ml) 1600 600 1400 500 1200 CD4 Cell Count (cells/mm 3 ) HIV-1 RNA (c/mL) 400 1000 800 300 600 200 400 100 200 80 c/mL 0 29-Nov-04 13-Dec-04 10-Jan-05 7-Mar-05 10-May-05 10-Jun-05 22-Aug-05 14-Nov-05 14-Dec-05 8-Feb-06 Previous ARV treatment: AZT + 3TC + IDV from April 1998 to October 2002 AZT/3TC + LPV/r from October 2002 to 13 December 2004 Viral load < 80 duplicates/mL since February 1999 Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Patient 2 – Low Level Viremia LPV/r monotherapy CD4 Cell Count (cells/mm 3 ) 80 c/mL 16-Sep-04 14-Oct-04 1-Dec-05 2-Mar-05 25-May-05 17-Aug-05 14-Sep-05 9-Nov-05 27-Jan-06 26-Apr-06 12-Jul-06 Adherence (cases number) 95% w4 98.9% w12 97.8% w24 99.4% w36 99.4% w48 100% w60 99% w72 98.3% w84 100% w96 Previous ARV treatment: AZT + ddI + RTV from September 1997 to May 2000 AZT + ddI + IDV/r from October 2002 to December 2001 AZT + ddI + NVP from December 2001 to September 2004 Viral load < 80 duplicates/ml since April 1998 Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Adverse Events No SAE 99% of the occasions were mellow to direct Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Triglycerides (mg/dL) 261 207 P = 0.229 Sample Size LPV/r MonoRx Control 30 28 26 Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Cholesterol (mg/dL) Total LDL HDL Sample Size LPV/r MonoRx Control 30 28 26 Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Anthropomethric Measurements Waist Thigh Arms Sample Size LPV/r MonoRx Control 30 28 26 Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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KALMO: Safety Results at Week 48 No measurably huge contrasts between arms as far as Lipid qualities Anthropometric estimations No clinically critical research centers variations from the norm Gastrointestinal occasions were more successive in the monotherapy aggregate (66.7% versus 16.7% of patients), exceptionally looseness of the bowels - 29 occasions in 19/30 patients (63.3%): mellow: 21 scenes direct: 7 scenes serious: 1 scene (LPV/r suspension) 5 treatment adjustments in triple arm for medication related toxicities 1 for bigotry to ddI 2 for lipodystrophy 1 for fringe neuropathy 1 for dyslipidemia Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Conclusions Diarrhea was more incessant in the monotherapy bunch There were 5 changes in ARV treatment because of poisonous quality on the control gather Rebound viremia in either arm was not related with the choice of resistance transformations In the one patient who fizzled LPV/r monotherapy, VL was re-supressed after heightening with Tenofovir + 3TC Switching from different HAART regimens to LPV/r monotherapy, in patients who were virologically smothered and without a background marked by past virologic disappointment, was powerful, protected and very much endured through 48 weeks Nunes EP. et al ., XVI IAC,Toronto , Canada, 2006; #TUAB0102 KalMo

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Acknowledgments Projeto Praça Onze: Mauro Schechter, Estevão Portela Nunes, Mônica Merçon, Roberto Zajdenverg, Jose Claudio Faulhaber, Regina Ferro do Lago, Mônica Barbosa, Carina Yoshida, Giselly Falco, Lucimar Salgado, Roberta Millan, Marcio Fernandes, Giovanna Ianini, Cynthia Ventura Hospital Geral de Nova Iguaçu: Marilia Santini de Oliveira, José Henrique Pilotto, Jorge Eurico Ribeiro, Lília Roy, Tânia Brum, Luciano Torres Souza, Ana Claudia Nunes Rodrigues, Andréa Gouveia, Luciane Viana And uncommonly the patients who take an interest in this review!

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